The Genetics of Alcohol Dependence: Twin and SNP-Based Heritability, and Genome-Wide Association Study Based on AUDIT Scores

H. Mbarek, Y. Milaneschi, I.O. Fedko, J.J. Hottenga, M.H.M. de Moor, R. Jansen, J. Gelernter, R. Sherva, G. Willemsen, D.I. Boomsma, B.W.J.H. Penninx, J.M. Vink

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Alcohol dependence (AD) is among the most common and costly public health problems contributing to morbidity and mortality throughout the world. In this study, we investigate the genetic basis of AD in a Dutch population using data from the Netherlands Twin Register (NTR) and the Netherlands Study of Depression and Anxiety (NESDA). The presence of AD was ascertained via the Alcohol Use Disorders Identification Test (AUDIT) applying cut-offs with good specificity and sensitivity in identifying those at risk for AD. Twin-based heritability of AD-AUDIT was estimated using structural equation modeling of data in 7,694 MZ and DZ twin pairs. Variance in AD-AUDIT explained by all SNPs was estimated with genome-wide complex trait analysis (GCTA). A genome-wide association study (GWAS) was performed in 7,842 subjects. GWAS SNP effect concordance analysis was performed between our GWAS and a recent AD GWAS using DSM-IV diagnosis. The twin-based heritability of AD-AUDIT was estimated at 60% (55-69%). GCTA showed that common SNPs jointly capture 33% (SE=0.12, P=0.002) of this heritability. In the GWAS, the top hits were positioned within four regions (4q31.1, 2p16.1, 6q25.1, 7p14.1) with the strongest association detected for rs55768019 (P=7.58×10
LanguageEnglish
Pages739-748
Number of pages10
JournalAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume168
Issue number8
DOIs
Publication statusPublished - 2015

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Genome-Wide Association Study
Alcoholism
Single Nucleotide Polymorphism
Alcohols
Netherlands
Genome
Diagnostic and Statistical Manual of Mental Disorders
Anxiety
Public Health
Depression
Morbidity
Sensitivity and Specificity
Mortality
Population

Cite this

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title = "The Genetics of Alcohol Dependence: Twin and SNP-Based Heritability, and Genome-Wide Association Study Based on AUDIT Scores",
abstract = "Alcohol dependence (AD) is among the most common and costly public health problems contributing to morbidity and mortality throughout the world. In this study, we investigate the genetic basis of AD in a Dutch population using data from the Netherlands Twin Register (NTR) and the Netherlands Study of Depression and Anxiety (NESDA). The presence of AD was ascertained via the Alcohol Use Disorders Identification Test (AUDIT) applying cut-offs with good specificity and sensitivity in identifying those at risk for AD. Twin-based heritability of AD-AUDIT was estimated using structural equation modeling of data in 7,694 MZ and DZ twin pairs. Variance in AD-AUDIT explained by all SNPs was estimated with genome-wide complex trait analysis (GCTA). A genome-wide association study (GWAS) was performed in 7,842 subjects. GWAS SNP effect concordance analysis was performed between our GWAS and a recent AD GWAS using DSM-IV diagnosis. The twin-based heritability of AD-AUDIT was estimated at 60{\%} (55-69{\%}). GCTA showed that common SNPs jointly capture 33{\%} (SE=0.12, P=0.002) of this heritability. In the GWAS, the top hits were positioned within four regions (4q31.1, 2p16.1, 6q25.1, 7p14.1) with the strongest association detected for rs55768019 (P=7.58×10",
author = "H. Mbarek and Y. Milaneschi and I.O. Fedko and J.J. Hottenga and {de Moor}, M.H.M. and R. Jansen and J. Gelernter and R. Sherva and G. Willemsen and D.I. Boomsma and B.W.J.H. Penninx and J.M. Vink",
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journal = "American Journal of Medical Genetics Part B: Neuropsychiatric Genetics",
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The Genetics of Alcohol Dependence: Twin and SNP-Based Heritability, and Genome-Wide Association Study Based on AUDIT Scores. / Mbarek, H.; Milaneschi, Y.; Fedko, I.O.; Hottenga, J.J.; de Moor, M.H.M.; Jansen, R.; Gelernter, J.; Sherva, R.; Willemsen, G.; Boomsma, D.I.; Penninx, B.W.J.H.; Vink, J.M.

In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Vol. 168, No. 8, 2015, p. 739-748.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Mbarek, H.

AU - Milaneschi, Y.

AU - Fedko, I.O.

AU - Hottenga, J.J.

AU - de Moor, M.H.M.

AU - Jansen, R.

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AU - Sherva, R.

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T2 - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

SN - 1552-4841

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